A dual crosslinked hydrogel-mediated integrated peptides and BMSC therapy for myocardial regeneration

Zheng, Zhoushun; Zheng, Gengfeng; Zhong, Fengmin; Wang, Bin; Liu, Li; Ma, Wei; Yu, Cui‐Yun; Wei, Hua

doi:10.1016/j.jconrel.2022.04.010

Cited by 23 publications

(15 citation statements)

References 53 publications

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“…The MI rat model was constructed by ligating the proximal left anterior descending branch of the artery according to the reported procedures. [ 34 ] Following artery ligation, hydrogel was injected into the infarcted area and five surrounding regions (20 µL per region) (Figure S15, Supporting Information). Eight rats died during the construction of the infarct model and subsequent survival during the course of the experiments (Figure S16, Supporting Information).…”

Section: Methodsmentioning

confidence: 99%

“…The MI rat model was constructed by ligating the proximal left anterior descending branch of the artery according to the reported procedures. [34] Following artery ligation, hydrogel was injected into Detection of Apoptosis at the Infarcted Area: 3 days after surgery, normal or infarcted hearts from the sham, saline, and hydrogel-treated groups were collected and fixed in 4% (w/v) formaldehyde, paraffin-embedded, and sectioned. TUNEL was used to stain apoptotic cells, 𝛼-actinin was used to stain the cardiac cytoskeleton, and DAPI was used to stain the nucleus.…”

Section: Methodsmentioning

confidence: 99%

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A ROS‐Responsive Liposomal Composite Hydrogel Integrating Improved Mitochondrial Function and Pro‐Angiogenesis for Efficient Treatment of Myocardial Infarction

Zheng

Cai

Liu

et al. 2022

Adv Healthcare Materials

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Mitochondrial dysfunction of cardiomyocytes (CMs) has been identified as a significant pathogenesis of early myocardial infarction (MI). However, only a few agents or strategies have been developed to improve mitochondrial dysfunction for the effective MI treatment. Herein, a reactive oxygen species (ROS)-responsive PAMB-G-TK/4-arm-PEG-SG hydrogel is developed for localized drug-loaded liposome delivery. Notably, the liposomes contain both elamipretide (SS-31) and sphingosine-1-phosphate (S1P), where SS-31 acts as an inhibitor of mitochondrial oxidative damage and S1P as a signaling molecule for activating angiogenesis. Liposome-encapsulated PAMB-G-TK/4-arm-PEG-SG hydrogels demonstrate myocardium-like mechanical strength and electrical conductivity, and ROS-sensitive release of SS-31 and S1P-loaded liposomes. Further liposomal release of SS-31, which can target cytochrome c in the mitochondrial inner membrane of damaged CMs, inhibits pathological ROS production, improving mitochondrial dysfunction. Meanwhile, S1P released from the liposome induces endothelial cell angiogenesis by activating the S1PR1/PI3K/Akt pathway. In a rat MI model, the resulting liposomal composite hydrogel improves cardiac function by scavenging excess ROS, improving mitochondrial dysfunction, and promoting angiogenesis. This study reports for the first time a liposomal composite hydrogel that can directly target mitochondria of damaged CMs for a feedback-regulated release of encapsulated liposomes to consume the overproduced pathological ROS for improved CM activity and enhanced MI treatment.

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Section: Methodsmentioning

confidence: 99%

“…The MI rat model was constructed by ligating the proximal left anterior descending branch of the artery according to the reported procedures. [34] Following artery ligation, hydrogel was injected into Detection of Apoptosis at the Infarcted Area: 3 days after surgery, normal or infarcted hearts from the sham, saline, and hydrogel-treated groups were collected and fixed in 4% (w/v) formaldehyde, paraffin-embedded, and sectioned. TUNEL was used to stain apoptotic cells, 𝛼-actinin was used to stain the cardiac cytoskeleton, and DAPI was used to stain the nucleus.…”

Section: Methodsmentioning

confidence: 99%

A ROS‐Responsive Liposomal Composite Hydrogel Integrating Improved Mitochondrial Function and Pro‐Angiogenesis for Efficient Treatment of Myocardial Infarction

Zheng

Cai

Liu

et al. 2022

Adv Healthcare Materials

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“…This composite scaffold possesses good bioactivity and structural features to improve the neocartilage restoration and the reconstruction of the osteochondral unit, which provides a promising opportunity for in situ cartilage regeneration due to the presence of TGF- β 1-simulating peptide in the structure of the hydrogel. Zheng et al developed a dual crosslinking conductive hydrogel containing modified hyaluronic acid (HA), gelatin (G), and Fe 3+ , demonstrating self-healing, degradable, and acceptable mechanical features adapted to the myocardial systolic-diastolic cycle resulting in a significant enhancement of the myocardial wall thickness, very similar to that of normal myocardium (by one time injection) [ 134 ]. This hydrogel contains a chemically conjugated-peptide sequence of GGR-KLT and was used for the encapsulation of bone mesenchymal stem cells (BMSCs), injected in a rat MI model.…”

Section: Biomedical Applications Of Peptide-based Hydrogelsmentioning

confidence: 99%

Peptide-Based Hydrogels: New Materials for Biosensing and Biomedical Applications

et al. 2022

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Peptide-based hydrogels have attracted increasing attention for biological applications and diagnostic research due to their impressive features including biocompatibility and biodegradability, injectability, mechanical stability, high water absorption capacity, and tissue-like elasticity. The aim of this review will be to present an updated report on the advancement of peptide-based hydrogels research activity in recent years in the field of anticancer drug delivery, antimicrobial and wound healing materials, 3D bioprinting and tissue engineering, and vaccines. Additionally, the biosensing applications of this key group of hydrogels will be discussed mainly focusing the attention on cancer detection.

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“…85 An integrated single "all-in-one" in situ dual cross-linking conductive hydrogel was constructed by mixing modified HA, gelatin and Fe 3+ , which provides mechanical and self-healing properties adapted to the cardiac systolic-diastolic cycle. 85 With oxygen-containing functional moieties like epoxy, carboxyl and hydroxyl groups, GO can improve mechanical properties of hydrogel substrates and the cellular behaviors including proliferation, adhesion, and differentiation, as demonstrated by the gelatin hydrogel scaffold cross-linked by genipin and incorporated with GO, which were endowed with desirable topographic morphology and mechanical support. 86 A 3D viscoelastic hydrogel embedding cardiomyocytes by the patch-clamp-in-gel technology has the capability to impose afterloads during constant cardiac contraction, which increased the transient outward K + current, elevated the L-type Ca 2+ current, decreased the inward rectifier K + current and prolonged the action potential duration.…”

Section: Conductivitymentioning

confidence: 99%

Insight into Heart-Tailored Architectures of Hydrogel to Restore Cardiac Functions after Myocardial Infarction

et al. 2022

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With permanent heart muscle injury or death, myocardial infarction (MI) is complicated by inflammatory, proliferation and remodeling phases from both the early ischemic period and subsequent infarct expansion. Though in situ re-establishment of blood flow to the infarct zone and delays of the ventricular remodeling process are current treatment options of MI, they fail to address massive loss of viable cardiomyocytes while transplanting stem cells to regenerate heart is hindered by their poor retention in the infarct bed. Equipped with heart-specific mimicry and extracellular matrix (ECM)-like functionality on the network structure, hydrogels leveraging tissue-matching biomechanics and biocompatibility can mechanically constrain the infarct and act as localized transport of bioactive ingredients to refresh the dysfunctional heart under the constant cyclic stress. Given diverse characteristics of hydrogel including conductivity, anisotropy, adhesiveness, biodegradability, self-healing and mechanical properties driving local cardiac repair, we aim to investigate and conclude the dynamic balance between ordered architectures of hydrogels and the post-MI pathological milieu. Additionally, our review summarizes advantages of heart-tailored architectures of hydrogels in cardiac repair following MI. Finally, we propose challenges and prospects in clinical translation of hydrogels to draw theoretical guidance on cardiac repair and regeneration after MI.

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A dual crosslinked hydrogel-mediated integrated peptides and BMSC therapy for myocardial regeneration

Cited by 23 publications

References 53 publications

A ROS‐Responsive Liposomal Composite Hydrogel Integrating Improved Mitochondrial Function and Pro‐Angiogenesis for Efficient Treatment of Myocardial Infarction

A ROS‐Responsive Liposomal Composite Hydrogel Integrating Improved Mitochondrial Function and Pro‐Angiogenesis for Efficient Treatment of Myocardial Infarction

Peptide-Based Hydrogels: New Materials for Biosensing and Biomedical Applications

Insight into Heart-Tailored Architectures of Hydrogel to Restore Cardiac Functions after Myocardial Infarction

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